Administration of a recombinant adenoviral vector expressing the Herpes simplex virus thymidine kinase gene (ADV-tk) followed by ganciclovir has been used in prior tirals that have produced encouraging results. This novel approach will be tested in a phase-I trial of escalating doses of ADV-tk delivered by intratumoral injection followed by a fixed dose of intravenous ganciclovir in patients with advanced non-small cell lung cancer. The starting dose of ADV-tk will be 1 x 108 pfu, which is well within the range tolerated in rodent and nonhuman primate studies. The ADV-tk dose will be escalated in cohorts of three patients each, as per standard phase-I procedure. Adverse event rates will be calculated based on person-time under observation stratified by dose escalation. Tumor volume will be calculated based on CT scan, and pre- and post-treatment differences will be determined. The Core Lab will process BAL and PBMC samples, collect 24 hour cell supernatants, store BAL fluid and cell supernatants, and perform RNA and DNA extractions The lab will also be used for ELISA and Northern analysis of IL-12 Rb2. The Center for AIDS Research (CFAR) Core Resource on flow cytometry will evaluate lymphocyte subtypes.